Background: Research on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential.
View Article and Find Full Text PDFObjectives: The main purpose of this research study was to compare mean modified straight-leg raise test (mSLR) and hamstring muscle length (HL) between chronic non-specific low back pain (LBP) and healthy subjects to understand the possibility of neuropathic causes in LBP population as it may impact the diagnosis and treatment of LBP. Another purpose was to compare mean mSLR between those with lumbar nerve root impingement and those without as determine by magnetic resonance imaging (MRI).
Methods: The design of the study is cross sectional and included 32 subjects with ages ranging from 18-50 years old.
Purpose: Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [ C]bicarbonate in the brain from hyperpolarized [1- C]pyruvate using carbon-13 ( C) MRI provides a unique opportunity for assessing PDH flux in vivo.
View Article and Find Full Text PDFImportance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.
Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.
The acute state of anorexia nervosa (AN) is associated with widespread reductions in cortical gray matter (GM) thickness and white matter (WM) volume, suspected changes in myelin content and elevated levels of the neuronal damage marker neurofilament light (NF-L), but the underlying mechanisms remain largely unclear. To gain a deeper understanding of brain changes in AN, we applied a multimodal approach combining advanced neuroimaging methods with analysis of blood-derived biomarkers. In addition to standard measures of cortical GM thickness and WM volume, we analyzed tissue-specific profiles of brain metabolites using multivoxel proton magnetic resonance spectroscopy, T1 relaxation time as a proxy of myelin content leveraging advanced quantitative MRI methods and serum NF-L concentrations in a sample of 30 female, predominately adolescent patients with AN and 30 age-matched female healthy control participants.
View Article and Find Full Text PDFThe prognostic ability of global white matter and gray matter metabolite ratios following pediatric traumatic brain injury (TBI) and their relationship to 12-month neuropsychological assessments of intelligence quotient (IQ), attention, and memory is presented. Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) in pediatric subjects with complicated mild (cMild), moderate, and severe TBI was acquired acutely (6-18 days) and 12 months post-injury and compared to age-matched typically developing adolescents. A global linear regression model, co-registering MRSI metabolite maps with 3D high-resolution magnetic resonance images, was used to identify longitudinal white matter and gray matter metabolite ratio changes.
View Article and Find Full Text PDFPurpose: [ C]Bicarbonate formation from hyperpolarized [1- C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of pyruvate and the integrity of mitochondrial function. The present study is to characterize the chronology of cerebral mitochondrial metabolism during secondary injury associated with acute traumatic brain injury (TBI) by longitudinally monitoring [ C]bicarbonate production from hyperpolarized [1- C]pyruvate in rodents.
Methods: Male Wistar rats were randomly assigned to undergo a controlled-cortical impact (CCI, n = 31) or sham surgery (n = 22).
Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings.
View Article and Find Full Text PDFProminence of cerebral veins using susceptibility weighted magnetic resonance imaging (SWI) has been used as a qualitative indicator of cerebral venous oxygenation (CvO). Quantitative susceptibility mapping (QSM) adds more precision to the assessment of CvO, but has not been applied to neonatal hypoxic ischemic injury (HII). QSM measures of venous susceptibility and their correlation with direct measures of brain oxygenation and cerebral blood flow (CBF) in the neonatal piglet.
View Article and Find Full Text PDFObjective: Our study addressed aims (1) to test the hypothesis that moderate-severe traumatic brain injury (TBI) in pediatric patients is associated with widespread white matter (WM) disruption, (2) to test the hypothesis that age and sex affect WM organization after injury, and (3) to examine associations between WM organization and neurobehavioral outcomes.
Methods: Data from 10 previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Pediatric Moderate/Severe TBI (msTBI) working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.
Proton (H) magnetic resonance spectroscopy provides a non-invasive and quantitative measure of brain metabolites. Traumatic brain injury impacts cerebral metabolism and a number of research groups have successfully used this technique as a biomarker of injury and/or outcome in both pediatric and adult TBI populations. However, this technique is underutilized, with studies being performed primarily at centers with access to MR research support.
View Article and Find Full Text PDF: Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor agonists including adrenocorticotropic hormone (ACTH) ameliorate inflammation and provide a novel therapeutic approach. We examined the effect of long-acting cosyntropin (CoSyn), a synthetic ACTH analog, on the early inflammatory response and functional outcome following experimental TBI.
View Article and Find Full Text PDFThis study is unique in that it examines the evolution of white matter injury very early and at 12 months post-injury in pediatric patients following traumatic brain injury (TBI). Diffusion tensor imaging (DTI) was acquired at two time-points: acutely at 6-17 days and 12 months following a complicated mild (cMild)/moderate (mod) or severe TBI. Regional measures of anisotropy and diffusivity were compared between TBI groups and against a group of age-matched healthy controls and used to predict performance on measures of attention, memory, and intellectual functioning at 12-months post-injury.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury-related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes.
View Article and Find Full Text PDFThis review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.
View Article and Find Full Text PDFFocal metabolic dysfunction commonly observed in temporal lobe epilepsy (TLE), and is associated with the development of medical intractability and neurocognitive deficits. It has not been established if this dysfunction is due to cell loss or biochemical dysfunction in metabolic pathways. To explore this question, dynamic H MRS following an infusion of [U- C] glucose was performed to measure glutamate (Glu) metabolism.
View Article and Find Full Text PDFNeuroimaging is commonly used for the assessment of children with traumatic brain injury and has greatly advanced how children are acutely evaluated. More recently, emphasis has focused on how advanced magnetic resonance imaging methods can detect subtler injuries that could relate to the structural underpinnings of the neuropsychological and behavioral alterations that frequently occur. We examine several methods used for the assessment of pediatric brain injury.
View Article and Find Full Text PDFResearch shows that approximately 14% of school age children with mild traumatic brain injury (TBI) including sports-related concussions (SRCs) remain symptomatic three months after injury. Advanced imaging studies early after injury have shown evidence of axonal damage, reduced N-acetyl aspartate (NAA) and impaired cerebral blood flow (CBF) in individuals with mild TBI. This study was undertaken to determine whether these techniques can provide valuable information in pediatric SRC patients with persistent post-concussive symptoms.
View Article and Find Full Text PDFThe present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of (13)C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how (13)C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury.
View Article and Find Full Text PDFIntroduction: Magnetic resonance imaging (MRI) and spectroscopy (MRS) have proven valuable in evaluating neonatal hypoxic-ischemic injury (HII).
Results: MRI scores in the basal ganglia of HII/HT(+) neonates were significantly lower than HII/HT(-) neonates, indicating less severe injury and were associated with lower discharge encephalopathy severity scores in the HII/HT(+) group (P = 0.01).
Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1.
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